Abstract: Peripheral artery disease (PAD) is associated with impaired leg function, possible limb loss and an increased risk of cardiovascular events. Intermittent claudication (IC) is a classic PAD symptom occurring in 40% of symptomatic patients, and is associated with 5-, and 15-year mortality rates of 30% and 70%, respectively. PAD is a debilitating illness affecting more than 8.5 million Americans of age 40 and older and 202 million people globally. Despite the high prevalence, PAD patients are less likely to receive appropriate treatment for their atherosclerotic risk factors than patients with coronary artery disease. Advances in endovascular therapy have reduced risks associated with intervention, enabling revascularization as a routine procedure in patients with lower extremity ischemia. However, revascularization success rates vary substantially and numerous PAD patients do not improve at 1-year despite technically good revascularization. Previous findings suggest that alterations in the microcirculation due to a paucity of collateralization may contribute to functional impairment in PAD patients. We hypothesize that the change in microvascular perfusion can identify PAD patients who do not improve at 12-months after revascularization. We will utilize contrast-enhanced magnetic resonance imaging (CE-MRI) to assess skeletal muscle perfusion in PAD patients. The CE-MRI measures will be associated with hemodynamics and symptoms. The early identification of individuals with a likely poor prognosis post intervention could help to improve surgical treatment strategies. We will investigate the association of microvascular perfusion (Aim 1) and measures of arterial hemodynamics (Aim 2) with leg function and PAD symptoms. We will utilize machine learning methodologies to identify predictors of poor leg function and symptoms (Aim 3). Given the high incidence of PAD and the associated high risk of cardiovascular events, it is paramount to identify individuals who are less likely to improve following lower extremity revascularization. The data of this clinical imaging study will provide novel information on the etiology of microvascular blood flow in PAD.